Respiratory muscle contractile inactivity induced by mechanical ventilation in piglets leads to leaky ryanodine receptors and diaphragm weakness

Matecki, Stéfan; Jung, Boris; Saint, Nathalie; Scheuermann, Valérie; Jaber, Samir; Lacampagne, Alain

doi:10.1007/s10974-017-9464-x

Cited by 13 publications

(13 citation statements)

References 42 publications

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“…Using a threshold of 7 µV and 12-h time period, the estimated time for resumption of a minimal EAdi was median (IQR) 18.40 (0.00-53.88) hours. Using a threshold of 5 µV, the time for resumption of EAdi for a 24-h and 12-h time period were 22.02 (0.00-50.77) h and 18.38 (0.00-53.88) h , respectively (Additional file 1: Table E3).…”

Section: Different Definitions For Eadi Resumptionmentioning

confidence: 99%

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients

et al. 2021

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Background In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity. Methods Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering. Results Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering. Conclusion Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

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Section: Different Definitions For Eadi Resumptionmentioning

confidence: 99%

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients

et al. 2021

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“…Increased expression levels of oxidative stress response genes, protein chaperones, and growth promoting factors in masticatory muscles were proposed to protect from, or compensate for the muscle atrophic stimuli [ 49 ]. Compared to hindlimb muscles, severe ventilator-induced diaphragmatic dysfunction was speculated to arise from sarcoplasmic reticulum ryanodine receptor remodeling and the abnormal sarcoplasmic reticulum Ca 2+ leakage at rest observed in the mechanically ventilated animals [ 52 ].…”

Section: Models Of Icuawmentioning

confidence: 99%

Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition

Lad

Saumur

Herridge

et al. 2020

IJMS

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Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.

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“…Impaired calcium homeostasis associated with a loss of diaphragm force but with no atrophy has been reported in the diaphragm during MV. 33,34 We therefore assessed the expression of the ryanodine receptor and the sarco(endo)plasmic calcium adenosine triphosphatase (SERCA) pumps in our model. Ryanodine Receptor.…”

Section: Assessment Of Calcium Homeostasismentioning

confidence: 99%

“…Several studies have pointed out impairment of calcium homeostasis in the diaphragm during MV. 33,34,41 They reported indirect evidence for enhanced intracellular calcium levels 41 and clear rapid remodeling of the ryanodine receptor 33,34 concomitant with a reduction of diaphragm force in the absence of atrophy or histologic injury. 33,52 In the current study, neither ryanodine receptor expression nor SERCA1 and SERCA2 expression were affected by dexmedetomidine, suggesting that alterations in calcium homeostasis were not involved in the loss of diaphragm force with dexmedetomidine.…”

Section: Dexmedetomidine Did Not Affect Calcium Homeostasismentioning

confidence: 99%

Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats

Breuer¹,

Berne

Rossaint³

et al. 2018

Anesthesiology

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V ENTILATOR-INDUCED diaphragmatic dysfunction (VIDD), which is defined as a time-dependent decrease of diaphragm strength after initiation of mechanical ventilation (MV), has been investigated for nearly two decades. 1 Studies in different species 2-4 and humans 5 revealed a loss of function and/or atrophy of the diaphragm with enhanced proteolysis, 6,7 autophagy, 8 and downregulation of protein synthesis 9 linked to oxidative stress. 10-12 Importantly, these effects develop immediately after the onset of MV. 13,14 VIDD may thus contribute to intensive care unit (ICU)-acquired diaphragm weakness, but other factors such as systemic inflammation and sepsis are playing an important role, too. 15-17 Since diaphragm dysfunction seems to influence the clinical outcome of mechanically ventilated patients with respiratory failure, especially in ICUs, 18-21 the importance of VIDD should not be neglected. What We Already Know about This Topic • Dexmedetomidine is a commonly used sedative in ventilated patents in intensive care units. It has complex effects on muscle metabolism and its effects on the diaphragm are poorly understood. What This Article Tells Us That Is New • After 24 h sedation in rats, dexmedetomidine (vs. pentobarbital) increased protein oxidation and impaired glucose transport and contractile force in the diaphragm, but did not cause atrophy. The impact on ventilator-induced diaphragmatic dysfunction and weaning requires study.

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Respiratory muscle contractile inactivity induced by mechanical ventilation in piglets leads to leaky ryanodine receptors and diaphragm weakness

Cited by 13 publications

References 42 publications

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients

Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition

Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats

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